The present application is a national phase application under 35 U.S.C §371 of International Application No. PCT/US2008/072686, filed Aug. 8, 2008, which claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 60/955,014, filed Aug. 9, 2007, the entire contents of each of which are hereby specifically incorporated by reference in their entirety.
1. Field of the Invention
The present invention generally relates to the fields of biomedical scaffolds, and methods of treating disease or disorders in a subject that involve implantation of the scaffolds set forth herein.
2. Description of Related Art
Considerable research has been reported over the last decade in the use of polymeric and ceramic biomaterials for producing scaffolds. However, the ideal material and fabrication technique for optimal bone tissue regeneration has yet to be identified. While current materials and techniques have met with varying successes, each material and/or technique exhibits limitations that must be addressed. In addition, there is an overall lack of success in bringing these technologies to the clinic, especially for the reconstruction and restoration of large bone defects.
Ideally, scaffolds for bone tissue regeneration should 1) exhibit biocompatibility without causing an inflammatory response or foreign body/toxic reaction, 2) have closely matched mechanical properties when compared to native bone, and 3) possess a mechanism to allow diffusion and/or transport of ions, nutrients, and wastes. Strong bonding with the host bone, active bone and vascular in-growth, and biodegradation of the scaffolds (depending on the applications) are equally desirable. Although the use of biodegradable polymer scaffolds has shown some success in terms of beneficial tissue in-growth, there are controversies over their use for bone regenerations. Limitations on the use of polymeric scaffolds have included the presence of hydrophobic surfaces which are not conducive for bone tissue regeneration and the lowering of localized pH during polymeric degradation. Restoration of bone function is also dependent on the closely-matched mechanical properties of the scaffold to the native bone. This mechanical similarity is important as bone is primarily load bearing in function with suitable load transfer necessary to regulate, adapt, and remodel bone during the normal healing process. Additionally, the architecture of the scaffolds (pore size, porosity, interconnectivity and permeability) needed for favorable ion and transport/diffusion of nutrients and wastes is generally perceived as critical for achieving sustained cell proliferation and differentiation within the scaffolds, thereby affecting function and restoration of the regenerated tissue. Although calcium phosphates have been used in the past for scaffold fabrication, different processes or procedures used have often resulted in calcium phosphate scaffolds with different architectures. As such, selection of a manufacturing process becomes important in dictating the scaffold architecture needed for successful bone tissue regeneration.
One example of scaffold architecture and its manufacture is set forth in Kawamura et al., U.S. Publ. Appl. No. 2006/0292350. One limitation of this invention is that it contains no functional interconnecting pore channels for cell migration, ion transport, or waste exchange. This is a limitation of a scaffold discussed by Takata et al., U.S. Pat. No. 4,629,464. Another example of scaffold architecture and its manufacture is set forth by Li et al., U.S. Publ. No. 2002/0037799. This invention is limited at least in part by the provision of only interconnecting pores for cell migration: no other migration means are provided. The scaffolds described by these references and others are limited in the degree of nutrient and ion transport to surrounding tissues. A need exists for the manufacture of scaffolds that better facilitate such transport to improve bone tissue regeneration.